This research will be done primarily in Botswana at the University of Botswana/Princess Marina Hospital in collaboration with Doreen Ramogola-Masire, as an extension of NIH Grant No. R01EB007594, 7-1-2008 to 6-30-2012. In 2007, cervical cancer accounted for over 24% of all cancers among women in Botswana. With studies establishing HIV as a cofactor in the development of HPV and cervical neoplasia and the incidence of HIV/AIDS in the country continuing to rise, early diagnosis of cervical cancer and its precursors is a key priority. This proposal integrates a series of collaborative studies to develop, test, and implement optical imaging technologies to improve cervical cancer screening in Botswana. In Aim 1, we will jointly develop a wide-field imaging system designed specifically to image the cervix. We will combine this system with a high-resolution microendoscope developed under the parent NIH grant to form a multimodal imaging platform. Members of Dr. Richards-Kortum's research group will travel to work with local biomedical engineers at the Princess Marina Hospital to assemble the imaging platform in Botswana, establishing the necessary infrastructure and expertise to build, test, and maintain optical imaging systems on-site. In Aim 2, Dr. Doreen Ramogola-Masire, an obstetrician gynecologist with extensive experience establishing and managing cancer screening programs in Africa, will lead a pilot clinical study to test these systems in Botswana, collecting wide-field and high-resolution image data in reflectance and fluorescence modes. In Aim 3, we will work together to analyze the clinical data to establish the imaging mode, or combination of modes which demonstrate the highest degree of correlation with disease state. This information will be used to generate image overlay maps to visually indicate the probability of disease, aimed at assisting the non-specialist healthcare provider in clinical decision making. Our long-term hypothesis is that quantitative, digital wide-field imaging combined with high-resolution cellular imaging will assist in the early detection of cervical cancer through improved screening in developing countries such as Botswana.